GeneBe

rs199934107

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_145045.5(ODAD3):​c.1203G>A​(p.Arg401=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,611,840 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

ODAD3
NM_145045.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.19
Variant links:
Genes affected
ODAD3 (HGNC:28303): (outer dynein arm docking complex subunit 3) This gene encodes a protein containing coiled-coil domains. The encoded protein functions in outer dynein arm assembly and is required for motile cilia function. Mutations in this gene result in primary ciliary dyskinesia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 19-11422775-C-T is Benign according to our data. Variant chr19-11422775-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.18 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0025 (381/152346) while in subpopulation AFR AF= 0.00858 (357/41586). AF 95% confidence interval is 0.00785. There are 1 homozygotes in gnomad4. There are 167 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ODAD3NM_145045.5 linkuse as main transcriptc.1203G>A p.Arg401= synonymous_variant 9/13 ENST00000356392.9 NP_659482.3
ODAD3NM_001302453.1 linkuse as main transcriptc.1041G>A p.Arg347= synonymous_variant 9/13 NP_001289382.1
ODAD3NM_001302454.2 linkuse as main transcriptc.1023G>A p.Arg341= synonymous_variant 7/11 NP_001289383.1
ODAD3XM_017026241.2 linkuse as main transcript downstream_gene_variant XP_016881730.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ODAD3ENST00000356392.9 linkuse as main transcriptc.1203G>A p.Arg401= synonymous_variant 9/131 NM_145045.5 ENSP00000348757 P2A5D8V7-1
ODAD3ENST00000591179.5 linkuse as main transcriptc.1023G>A p.Arg341= synonymous_variant 7/111 ENSP00000466800 A2
ODAD3ENST00000586836.5 linkuse as main transcriptc.630G>A p.Arg210= synonymous_variant 9/132 ENSP00000467429 A2
ODAD3ENST00000591345.5 linkuse as main transcriptc.*1122G>A 3_prime_UTR_variant, NMD_transcript_variant 10/145 ENSP00000467313

Frequencies

GnomAD3 genomes
AF:
0.00250
AC:
381
AN:
152228
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00861
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000982
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000725
AC:
175
AN:
241490
Hom.:
1
AF XY:
0.000576
AC XY:
76
AN XY:
131896
show subpopulations
Gnomad AFR exome
AF:
0.00951
Gnomad AMR exome
AF:
0.000436
Gnomad ASJ exome
AF:
0.00122
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000372
Gnomad OTH exome
AF:
0.000170
GnomAD4 exome
AF:
0.000303
AC:
442
AN:
1459494
Hom.:
2
Cov.:
32
AF XY:
0.000247
AC XY:
179
AN XY:
726108
show subpopulations
Gnomad4 AFR exome
AF:
0.0103
Gnomad4 AMR exome
AF:
0.000425
Gnomad4 ASJ exome
AF:
0.000727
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.000646
GnomAD4 genome
AF:
0.00250
AC:
381
AN:
152346
Hom.:
1
Cov.:
32
AF XY:
0.00224
AC XY:
167
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.00858
Gnomad4 AMR
AF:
0.000980
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00156
Hom.:
0
Bravo
AF:
0.00306
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 30 Benign:2
Likely benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesAug 21, 2023- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 19, 2024- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
CADD
Benign
6.2
DANN
Benign
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199934107; hg19: chr19-11533443; API